The objective of the proposed studies is to elucidate the relationship between the observed enzymatic deficiency of arginine esterase in patients with cystic fibrosis to the clinical manifestations of this disease. In order to accomplish this objective, it will be necessary to separate, purify, and characterize the various arginine esterases in normal plasma. Immunological techniques will be utilized to help define the relationships between the various arginine esterases in both normals, patients with cystic fibrosis, and obligate heterozygotes. The successful application of these techniques may well provide a specific biochemical marker which will be of value not only for the detection of cystic fibrosis but for the accurate identification of heterozygotes, the in utero detection of this disease, and possibly for the development of rational approaches to more precise therapy than exists at the present time. BIBLIOGRAPHIC REFERENCES: Shapira, E., Rao, G. J. S., Wessel, H. U., and Nadler, H. L.: Absence of an alpha-macroglobulin-protease complex in cystic fibrosis. Pediat. Res. 10:176, 1976. Shapira, E., Martin, C., and Nadler, H. L.: Functionally abnormal alpha2-macroglobulin in cystic fibrosis. Submitted for presentation at the annual meeting of the Society for Pediatric Research, San Francisco, April 25-30, 1977.